Method and apparatus for optimizing multi-site pacing using heart sounds

ABSTRACT

An example of a system for pacing through multiple electrodes in a ventricle includes a sensing circuit to sense cardiac signal(s), a pacing output circuit to deliver pacing pulses, a heart sound sensor to sense a heart sound signal, and a control circuit to control the delivery of the pacing pulses. The control circuit includes a heart sound detector to detect heart sounds using the heart sound signal, an electrical event detector to detect cardiac electrical events using the cardiac signal(s), a measurement module to measure an optimization parameter using the detected heart sounds, and an optimization module to approximately optimize one or more pacing parameters using the measured optimization parameter. The one or more pacing parameters include an electrode configuration parameter specifying one or more electrodes selected from the multiple electrodes in the ventricle for delivering ventricular pacing pulses to that ventricle.

CLAIM OF PRIORITY

This application claims the benefit of priority under 35 U.S.C. §119(e)of U.S. Provisional Patent Application Ser. No. 62/065,474, filed onOct. 17, 2014, which is herein incorporated by reference in itsentirety.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is related to commonly assigned U.S. Provisional PatentApplication Ser. No. 62/065,479, entitled “METHOD AND APPARATUS FORAMBULATORY OPTIMIZATION OF MULTI-SITE PACING USING HEART SOUNDS,” filedon Oct. 17, 2014, assigned to Cardiac Pacemakers, Inc., which is herebyincorporated by reference in its entirety.

TECHNICAL FIELD

This document relates generally to cardiac rhythm management and moreparticularly to method and apparatus for delivering pacing pulses tomultiple sites in at least one of the ventricles in a heart andoptimization of a pacing configuration.

BACKGROUND

The heart is the center of a person's circulatory system. It includes anelectro-mechanical system performing two major pumping functions. Theleft side of the heart, including the left atrium (LA) and the leftventricle (LV), draws oxygenated blood from the lungs and pumps it tothe organs of the body to supply their metabolic needs for oxygen. Theright side of the heart, including the right atrium (RA) and the rightventricle (RV), draws deoxygenated blood from the body organs and pumpsit to the lungs where the blood gets oxygenated. These pumping functionsresult from contractions of the myocardium (cardiac muscles). In anormal heart, the sinoatrial (SA) node, the heart's natural pacemaker,generates electrical impulses, called action potentials, that prop agatethrough an electrical conduction system to various regions of the heartand excite the myocardial tissues of these regions. Coordinated delaysin the propagations of the action potentials in a normal electricalconduction system cause the various portions of the heart to contract insynchrony and result in efficient pumping function.

A blocked or otherwise damaged electrical conduction system causesirregular contractions of the myocardium, a condition generally known asarrhythmia. Arrhythmia reduces the heart's pumping efficiency and hencediminishes the blood flow to the body. A deteriorated myocardium hasdecreased contractility, also resulting in diminished blood flow. Aheart failure patient usually suffers from both a damaged electricalconduction system and a deteriorated myocardium. Cardiac pacing therapyhas been applied to treat arrhythmia and heart failure. For example,cardiac resynchronization therapy (CRT) app lies left ventricular orbiventricular pacing to restore synchronized contractions. A CRT systemmay include electrodes placed in the RA, the RV, and the LV to deliverpacing pulses to one or more of these heart chambers for restoringcardiac synchrony by artificially coordinating atrioventricular and/orinterventricular myocardial activation delays.

SUMMARY

An example (e.g., “Example 1”) of a system for delivering pacing pulsesthrough a plurality of electrodes to a heart is provided. The heart hasfirst and second ventricles. The plurality of electrodes includes aplurality of first ventricular electrodes placed in or on the firstventricle. The system includes a cardiac sensing circuit, a pacingoutput circuit, a heart sound sensor, and a control circuit. The cardiacsensing circuit is configured to sense one or more cardiac signals. Thepacing output circuit is configured to deliver the pacing pulses. Theheart sound sensor is configured to sense a heart sound signal. Thecontrol circuit is configured to control the delivery of the pacingpulses using cardiac electrical events and a plurality of pacingparameters. The control circuit includes a heart sound detector, anelectrical event detector, a measurement module, and an optimizationmodule. The heart sound detector is configured to detect heart soundsusing the heart sound signal. The electrical event detector isconfigured to detect the cardiac electrical events using at least onecardiac signal of the sensed one or more cardiac signals. Themeasurement module configured to measure at least one optimizationparameter indicative of hemodynamic response to the delivery of thepacing pulses using the detected heart sounds. The optimization moduleis configured to approximately optimize one or more pacing parameters ofthe plurality pacing parameters using the measured at least oneoptimization parameter. The one or more pacing parameters include anelectrode configuration parameter specifying one or more firstventricular electrodes selected from the plurality of first ventricularelectrodes for delivering first ventricular pacing pulses of the pacingpulses to the first ventricle.

In Example 2, the subject matter of Example 1 may optionally beconfigured such that the one or more pacing parameters further includeone or more pacing timing parameters specifying timing of delivery ofthe first ventricular pacing pulses for each of the specified one ormore first ventricular electrodes.

In Example 3, the subject matter of Example 2 may optionally beconfigured such that the one or more pacing timing parameters includeone or more atrio-ventricular delays.

In Example 4, the subject matter of Example 2 may optionally beconfigured such that the one or more pacing timing parameters includeone or more intra-ventricular delays.

In Example 5, the subject matter of Example 2 may optionally beconfigured such that the one or more pacing timing parameters includeone or more inter-ventricular delays.

In Example 6, the subject matter of any one or any combination ofExamples 1-5 may optionally be configured such that the heart sounddetector is configured to detect first heart sounds (S1) using the heartsound signal, the measurement module is configured to measure an S1amplitude using the detected S1, and the optimization module isconfigured to approximately optimize the one or more pacing parametersfor maximizing the S1 amplitude.

In Example 7, the subject matter of any one or any combination ofExamples 1-6 may optionally be configured such that the heart sounddetector is configured to detect third heart sounds (S3) using the heartsound signal, the measurement module is configured to measure an S3amplitude using the detected S3, and the optimization module isconfigured to approximately optimize the one or more pacing parametersfor minimizing the S3 amplitude.

In Example 8, the subject matter of any one or any combination ofExamples 1-7 may optionally be configured such that the electrical eventdetector is configured to detect Q-waves or R-waves using the at leastone cardiac signal, the wherein the heart sound detector is configuredto detect first heart sounds (S1) using the heart sound signal, themeasurement module is configured to measure an pre-ejection period (PEP)as a time interval between a Q-wave or R-wave and a subsequentlyadjacent occurrence of the S1, and the optimization module is configuredto approximately optimize the one or more pacing parameters forminimizing the PEP.

In Example 9, the subject matter of any one or any combination ofExamples 1-8 may optionally be configured such that the heart sounddetector is configured to detect first heart sounds (S1) and secondheart sounds (S2) using the heart sound signal, the measurement moduleis configured to measure an ejection time (ET) as a time intervalbetween an occurrence of the S1 and a subsequently adjacent occurrenceof the S2, and the optimization module is configured to approximatelyoptimize the one or more pacing parameters for maximizing the ET.

In Example 10, the subject matter of any one or any combination ofExamples 1-7 may optionally be configured such that the electrical eventdetector is configured to detect Q-waves or R-waves using the at leastone cardiac signal, the wherein the heart sound detector is configuredto detect first heart sounds (S1) and second heart sounds (S2) using theheart sound signal, the measurement module is configured to measure anpre-ejection period (PEP) as a time interval between a Q-wave or R-waveand a subsequently adjacent occurrence of the S1 and measure an ejectiontime (ET) as a time interval between an occurrence of the S1 and asubsequently adjacent occurrence of the S2, and the optimization moduleis configured to approximately optimize the one or more pacingparameters for minimizing a ratio of the PEP to the ET.

In Example 11, the subject matter of any one or any combination ofExamples 1-10 may optionally be configured such that the electricalevent detector is configured to detect R-waves using the at least onecardiac signal, the wherein the heart sound detector is configured todetect second heart sounds (S2) using the heart sound signal, themeasurement module is configured to measure an R-S2 interval between anR-wave and a subsequently adjacent occurrence of the S2, and theoptimization module is configured to approximately optimize the one ormore pacing parameters for minimizing the R-S2 interval.

In Example 12, the subject matter of any one or any combination ofExamples 1-11 may optionally be configured to include an implantablemedical device and a first implantable ventricular lead. The implantablemedical device includes at least the cardiac sensing circuit, the pacingoutput circuit, and the control circuit. The first implantableventricular lead is configured to be coupled to the implantable medicaldevice and including the plurality of first ventricular electrodes.

In Example 13, the subject matter of Example 12 may optionally beconfigured such that the first implantable ventricular lead is animplantable left ventricular lead.

In Example 14, the subject matter of Example 12 may optionally beconfigured such that the first implantable ventricular lead is animplantable right ventricular lead.

In Example 15, the subject matter of any one or any combination ofExamples 12-14 may optionally be configured to further include an atriallead and a second ventricular lead. The atrial lead is configured to becoupled to the implantable medical device and including one or moreatrial electrodes. The second ventricular lead configured to be coup ledto the implantable medical device and including one or more secondventricular electrodes.

An example of a method (e.g., “Example 16”) for pacing a heart havingfirst and second ventricles is also provided. The method includesdelivering pacing pulses to the heart through at least a plurality offirst ventricular electrodes placed in or on the first ventricle,sensing one or more cardiac signals indicative of cardiac electricalevents, sensing a heart sound signal indicative of heart sounds,measuring at least one optimization parameter indicative of hemodynamicresponse to the delivery of the pacing pulses using at least the heartsound signal, approximately optimizing one or more pacing parameters ofa plurality of pacing parameters using the measured at least oneoptimization parameter, and controlling the delivery of the pacingpulses using the cardiac electrical events and the plurality of pacingparameters. The one or more pacing parameters includes an electrodeconfiguration parameter specifying one or more first ventricularelectrodes selected from the plurality of first ventricular electrodesfor delivering first ventricular pacing pulses of the pacing pulses tothe first ventricle.

In Example 17, the subject matter of the one or more pacing parametersas found in Example 16 may optionally further include one or more pacingtiming parameters specifying timing of delivery of the first ventricularpacing pulses for each of the specified one or more first ventricularelectrodes.

In Example 18, the subject matter of any one or any combination ofExamples 16 and 17 may optionally include measuring a first heart sound(S1) amplitude using the hearing sound signal and approximatelyoptimizing the one or more pacing parameters for maximizing the S1amplitude.

In Example 19, the subject matter of any one or any combination ofExamples 16-18 may optionally include measuring a third heart sound (S3)amplitude using the hearing sound signal and approximately optimizingthe one or more pacing parameters for minimizing the S3 amplitude.

In Example 20, the subject matter of any one or any combination ofExamples 16-19 may optionally include measuring a pre-ejection period(PEP) using the one or more cardiac signals and the hearing sound signaland approximately optimizing the one or more pacing parameters forminimizing the PEP.

In Example 21, the subject matter of any one or any combination ofExamples 16-20 may optionally include measuring an ejection time (ET)using the hearing sound signal and approximately optimizing the one ormore pacing parameters for maximizing the ET.

In Example 22, the subject matter of any one or any combination ofExamples 16-19 may optionally include measuring a pre-ejection period(PEP) using the one or more cardiac signals and the hearing soundsignal, measuring an ejection time (ET) using the hearing sound signal,and approximately optimizing the one or more pacing parameters forminimizing a ratio of the PEP to the ET.

In Example 23, the subject matter of any one or any combination ofExamples 16-22 may optionally include measuring an R-S2 interval betweena ventricular depolarization (R-wave) and a subsequently adjacentoccurrence of sound heart sound (S2) using the one or more cardiacsignals and the hearing sound signal, and approximately optimizing theone or more pacing parameters for minimizing the R-S2 interval.

This Summary is an overview of some of the teachings of the presentapplication and not intended to be an exclusive or exhaustive treatmentof the present subject matter. Further details about the present subjectmatter are found in the detailed description and app ended claims. Otheraspects of the disclosure will be apparent to persons skilled in the artupon reading and understanding the following detailed description andviewing the drawings that form a part thereof, each of which are not tobe taken in a limiting sense. The scope of the present disclosure isdefined by the appended claims and their legal equivalents.

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings illustrate generally, by way of example, variousembodiments discussed in the present document. The drawings are forillustrative purposes only and may not be to scale.

FIG. 1 is an illustration of an embodiment of a cardiac rhythmmanagement (CRM) system and portions of an environment in which the CRMsystem is used.

FIG. 2 is a block diagram illustrating an embodiment of a multi-sitepacing (MSP) circuit of an implantable medical device (IMD) of the CRMsystem.

FIG. 3 is a block diagram illustrating an embodiment of the CRM system.

FIG. 4 is a flow chart illustrating an embodiment of a method fordelivering cardiac pacing including an acute optimization procedure forapproximately optimizing MSP.

FIG. 5 is a flow chart illustrating an embodiment of a method forexecuting an MSP optimization protocol.

FIG. 6 is a block diagram illustrating another embodiment of the MSPcircuit.

FIG. 7 is a flow chart illustrating an embodiment of a method fordelivering cardiac pacing including the acute optimization procedure forapproximately optimizing MSP and an ambulatory optimization procedurefor approximately re-optimizing the MSP.

FIG. 8 is a flow chart illustrating an embodiment of a method forinitiating the ambulatory optimization procedure.

FIG. 9 is an illustration of an example of comparing an MSPconfiguration to a single-site pacing configuration.

DETAILED DESCRIPTION

In the following detailed description, reference is made to theaccompanying drawings which form a part hereof, and in which is shown byway of illustration specific embodiments in which the invention may bepracticed. These embodiments are described in sufficient detail toenable those skilled in the art to practice the invention, and it is tobe understood that the embodiments may be combined, or that otherembodiments may be utilized and that structural, logical and electricalchanges may be made without departing from the spirit and scope of thepresent invention. The following detailed description provides examples,and the scope of the present invention is defined by the appended claimsand their legal equivalents.

It should be noted that references to “an”, “one”, or “various”embodiments in this disclosure are not necessarily to the sameembodiment, and such references contemplate more than one embodiment.

This document discusses a method and system for multi-site pacing(“MSP”) that includes optimization of the pacing parameters using heartsounds. The system is configured to deliver pacing pulses to a patient'sheart. The patient's heart includes the right atrium (RA), the rightventricle (RV), the left atrium (LA), and the left ventricles. In thisdocument, “multi-site pacing”, or “MSP”, includes delivering pacingpulses to a plurality of pacing sites in the patient's heart with thedelivery to each site of the plurality of pacing sites individuallycontrollable, and the plurality of pacing sites includes at least twopacing sites in the LV, at least two pacing sites in the RV, or at leasttwo pacing sites in each of the LV and RV. “Single-site pacing” includesdelivering pacing pulses to one or more pacing sites in the patient'sheart with the delivery to each site of the one or more pacing sitesindividually controllable, and the one or more pacing sites include onepacing sites in the LV, one pacing site in the RV, or one pacing site ineach of the LV and RV of the patient's heart. A pacing electrode isplaced at each pacing site of the plurality of pacing sites. Thedelivery to each site of the plurality of pacing sites is individuallycontrollable as, for example, the at least two sites in one ventricularcan be paced at different times (e.g., with an inter-site orinter-electrode delay) during each cardiac cycle. An “MSP system”includes a pacing system that can be programmed for MSP or single-sitepacing.

Cardiac resynchronization therapy (“CRT”) has been applied to treatheart failure patient. An implantable CRT system may include, forexample, an implantable biventricular pacing device that delivers pacingpulses to a pacing site in each of the RV and the LV through a leadincluding an electrode placed at the pacing site. It has been learnedthat effectiveness of such biventricular pacing therapy in treatingheart failure in a patient may depend on the locations of the pacingsites, i.e., where the electrodes are placed in the RV and the LV. Theoptimal locations may change as the condition of the patient's heartchanges. After the implantation of the leads with the electrodes placedat the pacing sites, however, the locations of the pacing sites cannotbe adjusted. It has also been learned that a single pacing site in aventricle, even when optimally located, may not produce the desirablepattern of activation of that ventricle.

The present system can include an implantable MSP device that can beprogrammed to deliver pacing pulses to multiple pacing sites in at leastone of the ventricles of the patient's heart, using at least oneimplantable lead including multiple electrodes each placed on one pacingsite of the multiple pacing sites. When being configured to treat heartfailure patients by restoring synchrony in cardiac contractions, the MSPmay be referred to as multi-site CRT. In various embodiments, theprobability of delivering pacing pulses to an efficient pacing site in aventricle can be increased by increasing the number of pacing sites inthat ventricle. The efficient pacing site is the pacing site (electrodelocation) that allows the delivery of the pacing pulses to produce theintended effect. In various embodiments, faster and more physiologicactivation of a ventricle can be achieved by delivering pacing pulses tomore pacing sites (electrode locations) in the ventricle. Afterimplantable of the implantable MSP device and the implantable lead, themultiple electrodes allow for selection of one or more pacing sites inthe ventricle where the multiple electrodes are placed. In variousembodiments, the efficacy of the MSP delivered from such a systemdepends on, among other things, the selection of pacing sites in theheart and the relative timing of pacing in those pacing sites(inter-site or inter-electrode pacing delays). Thus, optimization of theMSP may include optimizing the selection of the pacing sites and thetiming of pacing in each selected pacing site. For the ventricle inwhich the multiple electrodes are placed, the optimization can identifyan approximately optimal electrode set, which can include one or moreelectrodes (each corresponding to a pacing site), and determine timingof delivering the pacing pulses to each electrode of the identifiedapproximately optimal electrode set. In various embodiments, theoptimization can include comparison among various electrodes insingle-site pacing, various electrodes in MSP, and various multi-siteactivation delay options.

In various embodiments, the performance of the MSP can be evaluated andoptimized using heart sounds. Heart sounds include the “first heartsound” or S1, the “second heart sound” or S2, the “third heart sound” orS3, the “fourth heart sound” or S4, and their various sub-components. S1is known to be indicative of, among other things, mitral valve closure,tricuspid valve closure, and aortic valve opening. S2 is known to beindicative of, among other things, aortic valve closure and pulmonaryvalve closure. S3 is known to be a ventricular diastolic filling soundoften indicative of certain pathological conditions including heartfailure. S4 is known to be a ventricular diastolic filling soundresulted from atrial contraction and is usually indicative ofpathological conditions. The term “heart sound” hereinafter refers toany heart sound (e.g., S1) and any components thereof (e.g., M1component of S1, indicative of Mitral valve closure). In this document,“heart sound” includes audible and inaudible mechanical vibrationscaused by cardiac activity that can be sensed with an accelerometer ormicrophone. Accordingly, the scope of “acoustic energy” in this documentextends to energies associated with such mechanical vibrations. Unlessnoted otherwise, S1, S2, S3, and S4 refer to the first, second, third,and fourth heart sounds, respectively, as a heart sound type, or as oneor more occurrences of the corresponding type heart sounds, depending onthe context.

In this document, “user” includes a physician or other caregiver whoexamines and/or treats a patient using one or more of the methods andapparatuses reported in the present document.

To treat heart failure, various parameters indicative of status of heartfailure in a patient, such as one or more parameters indicative of thepatient's hemodynamic response to cardiac pacing, are measured using atleast heart sounds. In some embodiments, various parameters indicativeof status of heart failure in the patient are measured using both heartsounds and cardiac electrical events. Examples of parameters indicativeof the patient's hemodynamic response to cardiac pacing include systolictime intervals (STIs) that may be measured between cardiac electricaland/or mechanical events related to systole and diastolic time intervals(DTIs) that may be measured between cardiac electrical and/or mechanicalevents related to diastole. For example, as heart failure worsens,pre-ejection period (“PEP”) increases and ejection time (“ET”)decreases. STIs and DTIs can be determined using pressure waveforms, butcan also be estimated using heart sound waveforms. The time intervalbetween the Q or R-wave and the subsequently adjacent S1 can be anestimate of the PEP. The time interval between the S1 and thesubsequently adjacent S2 can be an estimate of the ET. Certain Heartsound amplitudes are also correlated to the worsening of heart failure.For example, diminishing of S1 amplitude may be indicative of weakeningof heart contractility (which can be measured by the rate of LV pressurechange, LV dP/dt), and S3 may be caused by elevation of filling pressureand/or stiffer ventricular wall, which are known to be associated withheart failure.

In various embodiments, the present system detects heart sounds andoptimizes MSP by adjusting one or more pacing parameters for one or moreof the following: (1) maximizing S1 amplitude, (2) minimizing S3amplitude, (3) minimizing paced PEP interval, (4) maximizing ET, (5)minimizing the ratio of PEP to ET, and (6) minimizing R-S2 interval (thetime interval between the R-wave and the subsequent occurrence of S2. Invarious embodiments, the present system detects diastolic interval (timeinterval between the S2 to the subsequently adjacent R-wave) andverifies that the detected diastolic interval is within an acceptablerange as a safety check. The adjustment of the one or more pacingparameters is limited by keeping the diastolic interval within theacceptable range.

In various embodiments, MSP can be optimized during and/or afterimplantation of the implantable MSP device and leads. In this document,optimization of MSP includes optimization of one or more pacingparameters in an MSP system that can be configured to MSP or single-sitepacing. The optimization of MSP may determine whether MSP or single-sitepacing should be applied, pacing sites, and timing parameters associatedwith each of the pacing sites. Thus, the optimization of MSP may resultin the optimal pacing configuration being a single-site pacingconfiguration.

Because the patient's heart failure status and/or other conditions maychange after the implantation, an implantable system cap able of MSP maybe prescribed even if single-site pacing is determined to be the optimalconfiguration at the time of the implantation. In various embodiments,the present system performs re-optimization of pacing parametersaccording to a predetermined schedule or as a need is indicated afterthe implantation of the implantable MSP device and leads.

In various embodiments, the present system adjusts the pacing parametersusing ambulatory optimization of MSP. The ambulatory optimization allowspacing parameters in an MSP system to be adjusted to approximatelymaximize benefit to the patient chronically. In various embodiments, anacute optimization of MSP is performed during, or upon completion of,the implantation of the implantable system, and ambulatory optimizationof MSP is performed thereafter. In one embodiment, the acuteoptimization and the ambulatory optimization (re-optimization) use thesame optimization procedure, such as when the optimization procedure isperformed using the implantable system. In another embodiment, the acuteoptimization and the ambulatory optimization (re-optimization) usedifferent optimization procedures, such as when the optimizationprocedure is performed using external sensor(s) and/or other deviceswhat may not be readily available during a re-optimization.

In one embodiment, a re-optimization of MSP is trigged using a timerprogrammed with a predetermined schedule, such as on a periodic basis.

In another embodiment, a re-optimization of MSP is trigged by adetection of a specified-type event. The specified-type event may beindicative of a change in the status of heart failure in the patient. Inone embodiment, an event that is indicative of worsening of the heartfailure is specified as an event that triggers the re-optimization ofMSP. In another embodiment, an event that is indicative of eitherworsening or improvement of a conduction associated with the patient'sheart failure may be specified as an event that triggers there-optimization of MSP if a change in the conduction suggests that thecurrent pacing parameters may no longer be approximately optimal. Invarious embodiments, the present system may include one or morespecified-type events each triggering the re-optimization of MSP.Examples of the one or more specified-type events detected using heartsounds include (1) a substantial decrease in S1 amplitude, (2) asubstantial change in S1 waveform morphology, (3) a substantial increasein S3 amplitude, (4) a substantial change in a systolic time interval,and (5) a substantial change in a diastolic time interval. Otherexamples of the one or more specified-type events include (1) asubstantial increase in an impedance phase loop area, (2) a substantialdecrease in the maximum rate of change in impedance (maximum dZ/dt), and(3) a substantial increase in QLV sensed as an interval between a globalpeak (e.g., a Q-wave on a surface electrocardiogram or unipolarventricular electrogram) and a local peak (an LV electrogram sensed atthe pacing site). In various embodiments, the specified-type events mayinclude any one or more events that can be indicative of a need for there-optimization of MSP.

In various embodiments, the one or more pacing parameters to be adjustedfor the optimization or re-optimization of MSP may include one or moreof electrode configuration (selection of electrodes for deliveringpacing), atrio-ventricular delay(s), interventricular delay(s),intraventricular delay(s), lower rate limit, and pacing threshold(s).The optimization of MSP in general may also include clinicalinterventions such as medication change. During the optimization orre-optimization of MSP, various pacing configurations (i.e., variouscombination of pacing parameters to be adjusted) are evaluated. In oneembodiment, the one or more pacing parameters to be adjusted for theoptimization or re-optimization of MSP are identified based on thepotential effect of each parameter in changing the status of heartfailure. In one embodiment, when a plurality of pacing parameters are tobe adjusted, they are evaluated one at a time, in the order of thepotential effect on the status of heart failure, with the pacingparameter identified to have the most significant effect in the statusof heart failure being evaluated first. The evaluation of each pacingparameter may include a forward or backward search, i.e., with the valueof that pacing parameter starting from the minimum and increaseincrementally, or starting from the maximum and decrease incrementally,with the change in the measure of heart failure status recorded for eachvalue evaluated.

FIG. 1 is an illustration of an embodiment of a cardiac rhythmmanagement (CRM) system 100 and portions of an environment in whichsystem 100 operates. CRM system 100 includes an implantable medicaldevice (IMD) 105 that is electrically coup led to a patient's heartthrough a lead system 108 including implantable leads 110, 115, and 125.An external system 190 communicates with IMD 105 via a telemetry link185. CRM system 100 is discussed by way of example and not by way oflimitation. In various embodiments, the present system can include anytypes of IMD and lead that can be configured to deliver MSP. Forexample, while the illustration embodiment allows for MSP pacing usingmultiple electrodes in the LV, various embodiments allow for MSP pacingusing multiple electrodes in either or both of the LV and RV.

IMD 105 includes a hermetically sealed can housing an electronic circuitthat senses physiological signals and delivers therapeutic electricalpulses. The hermetically sealed can also functions as an electrode(referred to as “the can electrode” hereinafter) for sensing and/orpulse delivery purposes. IMD 105 senses one or more cardiac signalsindicative of cardiac electrical events, including depolarization andrepolarization in each of the chambers (RA, RV, LA, and LV), andgenerates cardiac data representative of the one or more cardiacsignals. In one embodiment, IMD 105 includes a pacemaker that deliverscardiac pacing therapies. In another embodiment, IMD 105 includes thepacemaker and a cardioverter/defibrillator that deliverscardioversion/defibrillation therapies. In various embodiments, IMD 105includes one or more devices selected from monitoring devices andtherapeutic devices such as the pacemaker, thecardioverter/defibrillator, a neurostimulator, a drug delivery device,and a biological therapy device.

IMD 105 includes an MSP circuit 130 that is a pacing circuit capable ofMSP and can be programmed to deliver various cardiac pacing therapiesincluding MSP or single-site pacing. In various embodiments, MSP circuit130 can be programmed to provide multi-site or single-site CRT. Invarious embodiments, MSP circuit 130 senses a heart sound signal and useheart sounds to optimize cardiac pacing therapies including MSP. Variousembodiments of MSP circuit 130 are discussed below with reference toFIGS. 2-8.

Lead 110 is an RA pacing lead that includes an elongate lead body havinga proximal end 111 and a distal end 113. Proximal end 111 is coupled toa connector for connecting to IMD 105. Distal end 113 is configured forplacement in the RA in or near the atrial septum. Lead 110 includes anRA tip electrode 114A, and an RA ring electrode 114B. RA electrodes 114Aand 114B are incorporated into the lead body at distal end 113 forplacement in or near the atrial septum, and are each electrically coupled to IMD 105 through a conductor extending within the lead body. RAtip electrode 114A, RA ring electrode 114B, and/or the can electrodeallow for sensing an RA electrogram indicative of RA depolarizations(P-waves) and delivering RA pacing pulses.

Lead 115 is an RV pacing-defibrillation lead that includes an elongatelead body having a proximal end 117 and a distal end 119. Proximal end117 is coupled to a connector for connecting to IMD 105. Distal end 119is configured for placement in the RV. Lead 115 includes a proximaldefibrillation electrode 116, a distal defibrillation electrode 118, anRV tip electrode 120A, and an RV ring electrode 120B. Defibrillationelectrode 116 is incorporated into the lead body in a location suitablefor supraventricular placement in the RA and/or the superior vena cava(SVC). Defibrillation electrode 118 is incorporated into the lead bodynear distal end 119 for placement in the RV. RV electrodes 120A and 120Bare incorporated into the lead body at distal end 119. Electrodes 116,118, 120A, and 120B are each electrically coupled to IMD 105 through aconductor extending within the lead body. Proximal defibrillationelectrode 116, distal defibrillation electrode 118, and/or the canelectrode allow for delivery of cardioversion/defibrillation pulses tothe heart. RV tip electrode 120A, RV ring electrode 120B, and/or the canof IMD 105 allow for sensing an RV electrogram indicative of RVdepolarizations (R-waves) and delivering RV pacing pulses. In variousembodiments, proximal defibrillation electrode 116 and/or distaldefibrillation electrode 118 may also be used for sensing the RVelectrogram. It is noted that while the illustrated embodiment allowsfor cardioversion/defibrillation, various embodiments allow for MSPusing a system with or without cardioversion/defibrillation capabilities.

Lead 125 is an LV coronary pacing lead that includes an elongate leadbody having a proximal end 121 and a distal end 123. Proximal end 121 iscoupled to a connector for connecting to IMD 105. Distal end 123 isconfigured for placement in the coronary vein. Lead 125 includes aplurality of LV electrodes 128A-D. In the illustration embodiment, thedistal portion of lead 125 is configured for placement in the coronaryvein such that LV electrodes 128A-D are placed in the coronary vein. Inanother embodiment, the distal portion of lead 125 can be configured forplacement in the coronary sinus and coronary vein such that LVelectrodes 128A-D are placed in the coronary sinus and coronary vein. Invarious embodiments, lead 125 can be configured for LV electrodes 128A-Dto be placed in various locations in or on the LV for desirable patternof LV excitation using pacing pulses. LV electrodes 128A-D are eachincorporated into the distal portion of lead 125 and are eachelectrically coupled to IMD 105 through a conductor extending within thelead body. LV electrode 128A, LV electrode 128B, LV electrode 128C, LVelectrode 128D, and/or the can electrode allow for sensing an LVelectrogram indicative of LV depolarizations (R-Wave) and delivering LVpacing pulses.

Electrodes from different leads may also be used to sense an electrogramor deliver pacing or cardioversion/defibrillation pulses. For example,an electrogram may be sensed using an electrode selected from RVelectrode 116, 118, and 120A-B and another electrode selected from LVelectrode 128A-D. The lead configuration including RA lead 110, RV lead115, and LV lead 125 is illustrated in FIG. 1 by way of example and notby way of restriction. Other lead configurations may be used, dependingon monitoring and therapeutic requirements. For example, lead 115 maynot include defibrillation electrodes 116 and 118 when capability ofdelivering cardioversion/defibrillation therapy is not needed,additional leads may be used to provide access to additional cardiacregions, and leads 110, 115, and 125 may each include more or fewerelectrodes along the lead body at, near, and/or distant from the distalend, depending on specified monitoring and therapeutic needs. In variousembodiments, IMD 105 is programmable for sensing the one or more cardiacsignals and delivering pacing pulses using any combination ofelectrodes, such as those illustrated in FIG. 1, to accommodate variouspacing configurations as discussed in this document.

External system 190 allows for programming of IMD 105 and receivessignals acquired by IMD 105. In one embodiment, external system 190includes a programmer. In another embodiment, external system 190includes a patient monitoring system such as the system discussed belowwith reference to FIG. 3. In one embodiment, telemetry link 185 is aninductive telemetry link. In an alternative embodiment, telemetry link185 is a far-field radio-frequency telemetry link. Telemetry link 185provides for data transmission from IMD 105 to external system 190. Thismay include, for example, transmitting real-time physiological dataacquired by IMD 105, extracting physiological data acquired by andstored in IMD 105, extracting therapy history data stored in IMD 105,and extracting data indicating an operational status of IMD 105 (e.g.,battery status and lead impedance). The physiological data include thecardiac data representative of the one or more cardiac signals.Telemetry link 185 also provides for data transmission from externalsystem 190 to IMD 105. This may include, for example, programming IMD105 to acquire physiological data, programming IMD 105 to perform atleast one self-diagnostic test (such as for a device operationalstatus), programming IMD 105 to run a signal analysis algorithm (such asan algorithm implementing the tachyarrhythmia detection method discussedin this document), programming IMD 105 to deliver pacing and/orcardioversion/defibrillation therapies, and initiate an MSP optimizationprocedure in IMD 105 (as further discussed below).

FIG. 2 is a block diagram illustrating an embodiment of am MSP circuit230, which represents an embodiment of MSP circuit 130. MSP circuit 230includes a cardiac sensing circuit 232, a pacing output circuit 234, aheart sound sensor 236, and a control circuit 238. Cardiac sensingcircuit 232 senses one or more cardiac signals, such as intracardiacelectrograms, that are indicative of cardiac electrical events, usingleads such as those of lead system 108. Pacing output circuit 234delivers pacing pulses to the patient's heart though leads such as thoseof lead system 108. Heart sound sensor 236 senses a heart sound signalindicative of heart sounds. Examples of heart sound sensor 236 includeaccelerometer and microphone. In the illustrated embodiment, heart soundsensor 236 is housed in the hermetically sealed can of IMD 105. Inanother embodiment, heart sound sensor 236 can be external to the can,such as incorporated into one of the leads of lead system 108. Controlcircuit 238 controls the delivery of the pacing pulses using the sensedone or more cardiac signals and a plurality of pacing parameters. Invarious embodiments, pacing output circuit 234 includes a plurality ofpacing output channels each configured to deliver pacing pulses to apacing site of a plurality of pacing sites in the patient's heart, andcontrol circuit 234 controls delivery of a subset of the pacing pulsesfrom each channel of the plurality of pacing output channels using asubset of the plurality of pacing parameters for that channel.

Control circuit 238 includes an electrical event detector 240, a heartsound detector 242, a measurement module 244, and an optimization module246. Electrical event detector 230 detects specified-type cardiacelectrical events using at least one cardiac signal of the one or morecardiac signals sensed by cardiac sensing circuit 232, with the typespecified based on the need for the operation of optimization module246. Examples of the specified-type cardiac electrical event as neededfor optimizing MSP include the Q-waves and the R-waves.

Heart sound detector 242 detects specified-type heart sounds using theheart sound signal sensed by heart sound sensor 236, with the typespecified based on the need for the operation of optimization module246. Examples of the specific-type heart sounds include S1, S2, and S3.An example of a method and circuit for detecting S1, S2, and S3 arediscussed in U.S. Pat. No. 7,431,699, entitled, “METHOD AND APPARATUSFOR THIRD HEART SOUND DETECTION,” assigned to Cardiac Pacemakers, Inc.,which is incorporated herein by reference in its entirety.

Measurement module 244 measures at least one optimization parameterindicative of a status of heart failure (such as a parameter indicativeof the patient's hemodynamic response to cardiac pacing) using at leastone specified type of heart sounds detected by heart sound detector 242.In various embodiments, measurement module 244 measures one or moreoptimization parameters each indicative of the status of heart failure(such as one or more parameters indicative of the patient's hemodynamicresponse to cardiac pacing) using one or more specified types of heartsounds detected by heart sound detector 242 and/or one or more specifiedtypes of cardiac electrical events detected by electrical eventsdetector 240. Examples of such optimization parameters include (1) S1amplitude, such as the measured peak amplitude of the heart sound signalduring the detected S or the root-mean-square (RMS) value of themeasured peak amplitude, (2) S3 amplitude, such as the measured peakamplitude of the heart sound signal during the detected S3 or the RMSvalue of the measured peak amplitude, (3) PEP, such as estimated by themeasured time interval between the Q or R-wave and the subsequentlyadjacent S1, (4) ET, such as estimated by the measured time intervalbetween the S1 and the subsequently adjacent S2, and (5) R-S2 interval,which is the measured time interval between the R-wave and thesubsequent occurrence of S2. In one embodiment, the diastolic interval,such as estimated by the time interval between the S2 to thesubsequently adjacent R-wave, is measured by measurement module 244 forsafety check purposes.

Optimization module 246 performs an optimization procedure to optimizeMSP by approximately optimizing a pacing configuration in a systemcapable of delivering MSP. In this document, the “pacing configuration”is defined by one or more parameters approximately optimized by theoptimization procedure. In other words, the pacing configuration refersto the setting of the plurality of pacing parameters used forcontrolling the delivery of the pacing pulses, and an approximatelyoptimized pacing configuration refers to the setting of the plurality ofpacing parameters resulting from the optimization procedure. In variousembodiments, the optimization procedure approximately optimizes thepacing configuration by approximately optimizing one or more pacingparameters of the plurality of pacing parameters. In variousembodiments, the one or more pacing parameters to be approximatelyoptimized are selected based their potential impact on the patient'sheart failure status, such as on the patient's hemodynamic performance.

In various embodiments, the optimization procedure approximatelyoptimizes the one or more pacing parameters of the plurality pacingparameters using the at least one optimization parameter measured bymeasurement module 244. In various embodiments, the pacing pulses aredelivered through a plurality of electrodes to the patient's heart. Theplurality of electrodes includes a plurality of first ventricularelectrodes placed in or on the first ventricle of the patient's heart.The one or more parameters to be approximately optimized include anelectrode configuration parameter specifying one or more firstventricular electrodes selected from the plurality of first ventricularelectrodes for delivering first ventricular pacing pulses of the pacingpulses to the first ventricle. The first ventricle can be the LV or theRV. In the embodiment illustrated in FIG. 1, the first ventricle is theLV, the first ventricular electrodes includes LV electrodes 128A-D. Invarious embodiments, the one or more parameters to be approximatelyoptimized also include one or more pacing timing parameters specifyingtiming of delivery of the first ventricular pacing pulses for each ofthe specified one or more first ventricular electrodes. Examples of suchpacing timing parameters include one or more atrio-ventricular delays,one or more intra-ventricular delays, and one or more inter-ventriculardelays. In the embodiment illustrated in FIG. 1, examples ofatrio-ventricular delays include pacing time delays each between one ofRA electrodes 114A-B and one of LV electrodes 128A-D, examples ofintra-ventricular delays includes pacing time delays each between two ofLV electrodes 128A-D, and examples of inter-ventricular delays includepacing time delays each between one of RV electrodes 120A-B and one ofLV electrodes 128A-D.

In various embodiments, optimization 246 approximately optimizes thepacing configuration (i.e., the one or more pacing parameters) to (1)maximize S1 amplitude, (2) minimize S3 amplitude, (3) minimize paced PEPinterval, (4) maximize ET, (5) minimize the ratio of PEP to ET, and/or(6) minimize the R-S2 interval. In various embodiments, a plurality ofpacing configurations (different value sets for the one or more pacingparameters) is evaluated during the optimization procedure, and valuesof the at least one optimization parameter associated with each pacingconfiguration are measured by measurement module 244 and compared witheach other to result in the approximately optimal pacing configuration.In one embodiment, the optimization of the one or more pacing parametersis limited by keeping the diastolic interval within the acceptablerange.

FIG. 3 is a block diagram illustrating an embodiment of a CRM system300, which represents an embodiment of CRM system 100. CRM system 300includes leads 308, an IMD 305, and an external device 390. In variousembodiments, CRM system 300 allows for delivery of cardiac pacing pulsesto a plurality of pacing sites in the patient's heart.

In various embodiments, leads 308 include at least an atrial leadincluding one or more atrial electrodes and a first ventricular leadincluding a plurality of first ventricular electrodes. The firstventricular lead allows for delivering MSP. The one or more atrialelectrodes are each placed in an atrium. The first ventricularelectrodes are to be placed in a first ventricle, with each of theelectrodes placed in a first ventricular site of the plurality of pacingsites. In one embodiment, the atrium is the RA and the first ventricleis the LV. In another embodiment, the atrium is the RA and the firstventricle is the RV. In various embodiments, leads 308 includes a secondventricular lead including one or more second ventricular electrodes, inaddition to the atrial lead and the first ventricular lead. In oneembodiment, the first ventricular lead is an LV lead, and the secondventricular lead is an RV lead. In another embodiment, the firstventricular lead is an RV lead, and the second ventricular lead is an LVlead. Lead system 108 represents a specific example of leads 308, withlead 110 being the atrial lead, lead 125 being the first ventricularlead, and lead 115 being the second ventricular lead.

IMD 305 represents an embodiment of IMD 105 and includes MSP circuit130, a defibrillation circuit 380, and an implant telemetry circuit 382.Defibrillation circuit 380 delivers cardioversion/defibrillation pulsesto the patient heart through leads 308 when such capability is needed.Implant telemetry circuit 382 allows IMD 305 to communicate withexternal device 390 via telemetry link 185. In one embodiment, implanttelemetry circuit 382 receives the optimization command transmitted toIMD 305 for MSP circuit 130 to perform the optimization procedure foroptimizing MSP.

External device 390 represents an embodiment of external system 190. Inone embodiment, external device 390 includes a programmer for IMDs.External device 390 include a presentation device 394, a user inputdevice 396, and an external telemetry circuit 392. Presentation device394 presents various types of information to the user, such asinformation acquired by IMD 305, information indicative of operation ofIMD 305 including the current pacing configuration, and informationguiding the user to program IMD 305. User input device 396 receivesinputs from the user, such as commands controlling the representation ofinformation and commands for programming IMD 305, including theoptimization command. External telemetry circuit 382 allows externaldevice 390 to communicate with IMD 305 via telemetry link 185. In oneembodiment, upon reception of the optimization command by user inputdevice 396, external telemetry device 392 transmits the optimizationcommands to IMD 305.

FIG. 4 is a flow chart illustrating an embodiment of a method 400 fordelivering cardiac pacing including an acute optimization procedure forapproximately optimizing MSP. In one embodiment, MSP circuit 130 or 230is configured to perform method 400.

At 402, an implantable system programmable for delivering MSP isimplanted into a patient. Examples of such an implantable system areillustrated as IMD 105 with lead system 108 or IMD 305 with lead system308. At 404, pacing pulses are delivered to the patient's heart usingthe implanted system. At 406, an acute optimization procedure isperformed to identify an approximately optimal pacing configuration froma plurality of pacing configurations. The pacing configurations are eachdefined by at least one pacing parameter of a plurality of pacingparameters. In various embodiments, the approximately optimal pacingconfiguration is identified from a plurality of pacing configurationsevaluated during the acute optimization procedure. The plurality ofpacing configurations can be predefined and stored in the implantablesystem and/or dynamically defined based on outcome of the ongoingoptimization procedure. In various embodiments, the optimizationprocedure is performed by executing an optimization protocol, asdiscussed below with reference to FIG. 5. At 408, the plurality ofpacing parameters is set according to the identified approximatelyoptimal pacing configuration. At 410, the delivery of the pacing pulsesis controlled using the plurality of pacing parameters.

FIG. 5 is a flow chart illustrating an embodiment of a method 500 forexecuting an MSP optimization protocol. In one embodiment, method 500 isapplied to perform the acute optimization procedure at 406.

At 502, execution of the MSP optimization protocol is initiated inresponse to an optimization command. In one embodiment, when performingthe acute optimization procedure, the optimization command is entered bythe user using external system 190 such as external device 390.

At 504, pacing pulses are delivered using a pacing configuration of theplurality of pacing configurations. At 506, a value of at least oneoptimization parameter is measured while the pacing pulses are deliveredusing the pacing configuration. Examples of the at least oneoptimization parameter includes the S1 amplitude, S3 amplitude, PEP, ET,and R-S2 interval, as discussed above. In some embodiments, a pluralityof optimization parameters can be measured.

If the values of the at least one optimization parameter has beenmeasured for all the pacing configurations of the plurality of pacingconfigurations at 508, the measured values are compared to each other at510. At 512, an approximately optimal pacing configuration is selectedfrom the plurality of pacing configurations using an outcome of thecomparison. One example of the comparison and selection is discussedbelow with reference to FIG. 9.

If the value of the at least one optimization parameter needs to bemeasured for more pacing configurations of the plurality of pacingconfigurations at 508, the pacing pulses are delivered using the nextpacing configuration from the plurality of pacing configurations at 504,and this continues until the values of the at least one optimizationparameter has been measured for all the pacing configurations.

FIG. 6 is a block diagram illustrating an embodiment of the MSP circuit630, which represents another embodiment of MSP circuit 130 and afurther embodiment of MSP circuit 230. MSP circuit 630 includes cardiacsensing circuit 232, pacing output circuit 234, heart sound sensor 236,and a control circuit 638. In various embodiments, MSP 630 is configuredto perform the functions of MSP 230 and in addition, configured to allowfor ambulatory optimization of MSP.

Control circuit 638 includes an electrical event detector 640, a heartsound detector 642, a measurement module 644, an optimization module646, and an optimization initiator 648. In various embodiments,electrical event detector 640, heart sound detector 642, measurementmodule 644, and optimization module 646 perform the functions ofelectrical event detector 240, heart sound detector 242, measurementmodule 244, and optimization module 246, respectively, and are furtherconfigured to accommodate an ambulatory optimization procedure. Forexample, if the ambulatory optimization procedure requires measurementof an optimization parameter that is different from the at least oneoptimization parameter measured for the acute optimization procedure,control circuit 638 is configured to measure that different optimizationparameter and use it for the ambulatory optimization procedure. Invarious embodiments, the acute optimization procedure and the ambulatoryoptimization procedure may specify different pacing parameter(s) toapproximately optimize. In other embodiments, the acute optimizationprocedure and the ambulatory optimization procedure may specify the samepacing parameter(s) to approximately optimize. Examples for thespecified-type heart sounds, specified-type cardiac electrical events,optimization parameter, and one or more pacing parameters defining thepacing configuration are as discussed above for control circuit 238.Control circuit 230 and control circuit 638 may use same or differenttype(s) of heart sounds, same or different type(s) of cardiac electricalevents, same or different optimization parameter(s), and same ordifferent pacing configuration(s), such as selected from these examples.In other words, the acute optimization procedure and the ambulatoryoptimization procedure can use the same optimization protocol (method500) with the same parameters or different parameters. Control circuit638 is configured to accommodate both the acute optimization procedureand the ambulatory optimization procedure, and programmable for each ofthe acute optimization procedure and the ambulatory optimizationprocedure.

Optimization initiator 648 generates the optimization command, andoptimization initiator 648 performs the ambulatory optimizationprocedure in response to the optimization command. In variousembodiments, after an initial optimization of MSP using the acuteoptimization procedure, re-optimization of the MSP can be performedrepeatedly using the ambulatory optimization procedure. In variousembodiments, optimization initiator 648 generates the optimizationcommand in response to a user command, based on a predeterminedschedule, and/or based on re-optimization criteria. The user command maybe entered using external system 190, such discussed above for the acuteoptimization procedure. The predetermined schedule may specify a timeperiod for the to be performed on a periodic basis. The re-optimizationcriteria specify one or more types of event that triggers there-optimization.

In various embodiments, the one or more types of events specified in there-optimization criteria may each be indicative of a change in thestatus of heart failure in the patient. The change can be worsening orimprovement of the status of heart failure in a way that may suggest aneed for re-optimization of MSP. For example, an improvement of thestatus of heart failure may change the approximately optimal pacingconfiguration from an MSP pacing configuration to a single-site pacingconfiguration. Examples of such types of events include (1) asubstantial decrease in S1 amplitude (such as by at least 10%), (2) asubstantial change in paced S1 waveform morphology from a stored optimalpaced S1 waveform template (such as at least 10% change in at least onemorphological parameter measured from the paced S1 waveform), (3) asubstantial increase in S3 amplitude (such as by at least 5%), (4) asubstantial change in a systolic time interval (such as by at least 5%),and (5) a substantial change in a diastolic time interval (such as by atleast 5%). In various embodiments, the specified-type events may includeany one or more events that can be indicative of a need for there-optimization of MSP.

FIG. 7 is a flow chart illustrating an embodiment of a method 700 fordelivering cardiac pacing including the acute optimization procedure forapproximately optimizing MSP and an ambulatory optimization procedurefor approximately re-optimizing the MSP. In one embodiment, MSP circuit130 or 630 is configured to perform method 700.

At 702, an implantable system programmable for delivering MSP isimplanted into a patient. Examples of such an implantable system areillustrated as IMD 105 with lead system 108 or IMD 305 with lead system308. At 704, pacing pulses are delivered to the patient's heart usingthe implanted system. At 706, an acute optimization procedure isperformed to identify an approximately optimal pacing configuration froma plurality of pacing configurations. The pacing configurations are eachdefined by at least one pacing parameter of a plurality of pacingparameters. In various embodiments, the approximately optimal pacingconfiguration is identified from a plurality of pacing configurationsevaluated during the acute optimization procedure. The plurality ofpacing configurations can be predefined and stored in the implantablesystem and/or dynamically defined based on outcome of the ongoingoptimization procedure. In various embodiments, the optimizationprocedure is performed by executing an optimization protocol, asdiscussed above with reference to FIG. 5. At 708, the plurality ofpacing parameters is set according to the identified approximatelyoptimal pacing configuration. At 710, the delivery of the pacing pulsesis controlled using the plurality of pacing parameters.

At 712, an optimization command is received. The optimization command isto initiate a re-optimization of MSP by performing the ambulatoryoptimization procedure. At 714, the ambulatory optimization procedure isperformed to identify a new approximately optimal pacing configurationfrom the plurality of pacing configurations. In various embodiments, theoptimization procedure is performed by executing an optimizationprotocol, as discussed above with reference to FIG. 5. In variousembodiments, same or different type(s) of heart sounds, same ordifferent type(s) of cardiac electrical events, same or differentoptimization parameter(s), and same or different pacing configuration(s)may be used with the optimization protocol when execution for the acuteoptimization procedure and the ambulatory optimization procedure, suchas discussed above for control circuit 638.

If the new approximately optimal pacing configuration is the same as thecurrent pacing configuration (prior to the ambulatory optimizationprocedure) at 716, the delivery of the pacing pulses is continued to becontrolled using the current pacing configuration. If the newapproximately optimal pacing configuration differs from the currentpacing configuration at 716, the plurality of pacing parameters isadjusted according to the new approximately optimal pacing configurationat 718. The pacing pulses are continued to be delivered as controlledusing the adjusted pacing parameters.

FIG. 8 is a flow chart illustrating an embodiment of a method 800 forinitiating the ambulatory optimization procedure. Method 800 isperformed to produce the optimization command to be received at step 712of method 700. In one embodiment, optimization initiator 648 isconfigured to perform method 700.

At 802, the optimization command is generated according to apredetermined re-optimization schedule, such as on a periodic basis. At804, the optimization command is generated based on re-optimizationcriteria, such as by being triggered by a specified-type event. Examplesof the specified-type events include a substantial decrease in S1amplitude, a substantial change in paced S1 waveform morphology, asubstantial increase in S3 amplitude, a substantial change in a systolictime interval, and a substantial change in a diastolic time interval, asdiscussed above for optimization initiator 648. In various embodiments,the specified-type event may include any one or more events that can beindicative of a need for the re-optimization of MSP, which can bedetected from the heart sound signal or any other types of sensedsignals. At 806, the optimization command is received from a user. Thisprovides the user with the ability of initiate the ambulatoryoptimization procedure, for example, in response to an observed eventthat is not specified in the re-optimization criteria. In variousembodiments, any one or more of steps 802, 804, and 806 may be includedin method 800. At 808, the optimization protocol is executed in responseto the optimization command.

FIG. 9 is an illustration of an example of comparing an MSPconfiguration to a single-site pacing configuration. The pacing isdelivered to treat heart failure, including improving ventricularcontractility. The pacing configuration to be approximately optimized isdefined by at least an electrode configuration parameter. The systemused in the illustrated example includes at least two LV electrodes (LV1and LV2) and an RV electrode (RV1). The plurality of pacingconfigurations to be evaluated during the optimization of MSP includesLV2 only (LV single-site), LV1 and LV2 (LV multi-site), LV1 only (LVsingle-site), and RV1 and LV1 (BiV single-site).

To show the feasibility of optimizing MSP using heart sounds, the rateof change in LV pressure (LV dP/dt) is also determined for each of thepacing configurations at various atrioventricular (AV) delays. Theresults as seen in FIG. 9 show that the LV single-site pacing withelectrode LV1 provides the best performance as indicated by the LV dP/dt(at all AV delays) and by the largest S1 amplitude. This shown that thebest single-site pacing may be more efficient than an MSP configuration.An MSP system may provide the best long-term performance as the optimalpacing configuration may change over time as the patient's conditionschange. The present method and system as discussed this documents allowsthe MSP system to operate using an approximate optimal pacingconfiguration that is up dated to reflect the changes in the patient'scondition, among other things.

In various embodiments, the circuit of CRM system 100 may be implementedusing a combination of hardware and software. In various embodiments,each element of IMD 105 and external system 190, as illustrated in FIGS.1-3 and 6, including its various embodiments, may be implemented usingan application-specific circuit constructed to perform one or moreparticular functions or a general-purpose circuit programmed to performsuch function(s). For example, control circuit 238 and 638 may beimplemented using an application-specific circuit constructed to performone or more functions discussed as method(s) or method step (s) in thisdocument or a general-purpose circuit programmed to perform suchfunction(s). Such a general-purpose circuit includes, but is not limitedto, a microprocessor or a portion thereof, a microcontroller or portionsthereof, and a programmable logic circuit or a portion thereof.

It is to be understood that the above detailed description is intendedto be illustrative, and not restrictive. Other embodiments will beapparent to those of skill in the art upon reading and understanding theabove description. The scope of the invention should, therefore, bedetermined with reference to the appended claims, along with the fullscope of equivalents to which such claims are entitled.

What is claimed is:
 1. A system for delivering pacing pulses through aplurality of electrodes to a heart having first and second ventricles,the plurality of electrodes including a plurality of first ventricularelectrodes placed in or on the first ventricle, the system comprising: acardiac sensing circuit configured to sense one or more cardiac signals;a pacing output circuit configured to deliver the pacing pulses; a heartsound sensor configured to sense a heart sound signal; and a controlcircuit configured to control the delivery of the pacing pulses usingcardiac electrical events and a plurality of pacing parameters, thecontrol circuit including: a heart sound detector configured to detectheart sounds including second heart sounds (S2) using the heart soundsignal; an electrical event detector configured to detect the cardiacelectrical events including ventricular depolarization (R-waves) usingat least one cardiac signal of the sensed one or more cardiac signals; ameasurement module configured to measure at least one optimizationparameter indicative of hemodynamic response to the delivery of thepacing pulses using the detected heart sounds and to measure an S2-Rinterval between an occurrence of the S2 and a subsequently adjacentR-wave of the R-waves; and an optimization module configured to optimizeone or more pacing parameters of the plurality pacing parameters usingthe measured at least one optimization parameter while keeping the S2-Rinterval within an acceptable range, the one or more pacing parametersincluding an electrode configuration parameter specifying one or morefirst ventricular electrodes selected from the plurality of firstventricular electrodes for delivering first ventricular pacing pulses ofthe pacing pulses to the first ventricle using the measured at least oneoptimization parameter and one or more pacing timing parametersspecifying timing of the delivery of the first ventricular pacing pulsesdetermined for each electrode of the selected one or more firstventricular electrodes using the measured at least one optimizationparameter.
 2. The system of claim 1, wherein the heart sound detector isconfigured to detect first heart sounds (S1) using the heart soundsignal, the measurement module is configured to measure an S1 amplitudeusing the detected S1, and the optimization module is configured tooptimize the one or more pacing parameters for maximizing the S1amplitude.
 3. The system of claim 1, wherein the heart sound detector isconfigured to detect third heart sounds (S3) using the heart soundsignal, the measurement module is configured to measure an S3 amplitudeusing the detected S3, and the optimization module is configured tooptimize the one or more pacing parameters for minimizing the S3amplitude.
 4. The system of claim 1, wherein the electrical eventdetector is configured to detect Q-waves or R-waves using the at leastone cardiac signal, the heart sound detector is configured to detectfirst heart sounds (S1) using the heart sound signal, the measurementmodule is configured to measure an pre-ejection period (PEP) as a timeinterval between a Q-wave or R-wave and a subsequently adjacentoccurrence of the S1, and the optimization module is configured tooptimize the one or more pacing parameters for minimizing the PEP. 5.The system of claim 1, wherein the heart sound detector is configured todetect first heart sounds (S1) and second heart sounds (S2) using theheart sound signal, the measurement module is configured to measure anejection time (ET) as a time interval between an occurrence of the S1and a subsequently adjacent occurrence of the S2, and the optimizationmodule is configured to optimize the one or more pacing parameters formaximizing the ET.
 6. The system of claim 1, wherein the electricalevent detector is configured to detect Q-waves or R-waves using the atleast one cardiac signal, the heart sound detector is configured todetect first heart sounds (S1) and second heart sounds (S2) using theheart sound signal, the measurement module is configured to measure anpre-ejection period (PEP) as a time interval between a Q-wave or R-waveand a subsequently adjacent occurrence of the S1 and measure an ejectiontime (ET) as a time interval between an occurrence of the S1 and asubsequently adjacent occurrence of the S2, and the optimization moduleis configured to optimize the one or more pacing parameters forminimizing a ratio of the PEP to the ET.
 7. The system of claim 1,wherein the electrical event detector is configured to detect R-wavesusing the at least one cardiac signal, the heart sound detector isconfigured to detect second heart sounds (S2) using the heart soundsignal, the measurement module is configured to measure an R-S2 intervalbetween an R-wave and a subsequently adjacent occurrence of the S2, andthe optimization module is configured to optimize the one or more pacingparameters for minimizing the R-S2 interval.
 8. The system of claim 1,comprising: an implantable medical device including at least the cardiacsensing circuit, the pacing output circuit, and the control circuit; anda first implantable ventricular lead configured to be coupled to theimplantable medical device and including the plurality of firstventricular electrodes.
 9. The system of claim 8, wherein the firstimplantable ventricular lead is an implantable left ventricular lead.10. The system of claim 8, wherein the first implantable ventricularlead is an implantable right ventricular lead.
 11. The system of claim8, further comprising: an atrial lead configured to be coupled to theimplantable medical device and including one or more atrial electrodes;and a second ventricular lead configured to be coupled to theimplantable medical device and including one or more second ventricularelectrodes.
 12. A method for pacing a heart having first and secondventricles, the method comprising: delivering pacing pulses to the heartthrough at least a plurality of first ventricular electrodes placed inor on the first ventricle; sensing one or more cardiac signalsindicative of cardiac electrical events; sensing a heart sound signalindicative of heart sounds; measuring at least one optimizationparameter indicative of hemodynamic response to the delivery of thepacing pulses using at least the heart sound signal, including measuringan S2-R interval between an occurrence of sound heart sound (S2) and asubsequently adjacent ventricular depolarization (R-wave); andoptimizing one or more pacing parameters of a plurality of pacingparameters using the measured at least one optimization parameter,including: optimizing an electrode configuration parameter byidentifying one or more first ventricular electrodes from the pluralityof first ventricular electrodes for delivering first ventricular pacingpulses of the pacing pulses to the first ventricle using the measured atleast one optimization parameter; and optimizing one or more pacingtiming parameters by determining timing of the delivery of the firstventricular pacing pulses for each electrode of the selected one or morefirst ventricular electrodes using the measured at least oneoptimization parameter while keeping the S2-R interval within anacceptable range; and controlling the delivery of the pacing pulsesusing the cardiac electrical events and the plurality of pacingparameters.
 13. The method of claim 12, comprising: measuring a firstheart sound (S1) amplitude using the hearing sound signal; andoptimizing the one or more pacing parameters for maximizing the S1amplitude.
 14. The method of claim 12, comprising: measuring a thirdheart sound (S3) amplitude using the hearing sound signal; andoptimizing the one or more pacing parameters for minimizing the S3amplitude.
 15. The method of claim 12, comprising: measuring apre-ejection period (PEP) using the one or more cardiac signals and thehearing sound signal; and optimizing the one or more pacing parametersfor minimizing the PEP.
 16. The method of claim 12, comprising:measuring an ejection time (ET) using the hearing sound signal; andoptimizing the one or more pacing parameters for maximizing the ET. 17.The method of claim 12, comprising: measuring a pre-ejection period(PEP) using the one or more cardiac signals and the hearing soundsignal; measuring an ejection time (ET) using the hearing sound signal;and optimizing the one or more pacing parameters for minimizing a ratioof the PEP to the ET.
 18. The method of claim 12, comprising: measuringan R-S2 interval between a ventricular depolarization (R-wave) and asubsequently adjacent occurrence of sound heart sound (S2) using the oneor more cardiac signals and the hearing sound signal; and optimizing theone or more pacing parameters for minimizing the R-S2 interval.
 19. Themethod of claim 12, wherein delivering the pacing pulses to the heartcomprises delivering the pacing pulses to the heart from an implantablemedical device through an implantable left ventricular lead coupled tothe implantable medical device, the implantable left ventricular leadincluding the plurality of first ventricular electrodes placed in or ona left ventricle of the heart.
 20. The method of claim 12, whereindelivering the pacing pulses to the heart comprises delivering thepacing pulses to the heart from an implantable medical device through animplantable right ventricular lead coupled to the implantable medicaldevice, the implantable left ventricular lead including the plurality offirst ventricular electrodes placed in or on a right ventricle of theheart.